ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin

Clin Pharmacol Ther. 2008 Oct;84(4):457-61. doi: 10.1038/clpt.2008.25.

Abstract

ABCB1 haplotypes were determined in 534 healthy Finnish volunteers, of whom 24 participated in a pharmacokinetic study on simvastatin and atorvastatin. The frequencies of occurrence of haplotypes c.1236T-c.2677T-c.3435T and c.1236C-c.2677G-c.3435C were 42.7 and 34.4%, respectively. The simvastatin acid AUC(0-12h) was 60% larger, the atorvastatin AUC(0-infinity) 55% larger, and the atorvastatin half-life 24% longer in subjects with the ABCB1 TTT/TTT genotype (n = 12) than in those with the CGC/CGC genotype (n = 12) (P < 0.05), but there were no differences between the two genotypes with respect to the pharmacokinetics of the lactones of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Area Under Curve
  • Atorvastatin
  • Cross-Over Studies
  • Female
  • Finland
  • Half-Life
  • Haplotypes
  • Heptanoic Acids / pharmacokinetics*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Lactones / pharmacokinetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Pyrroles / pharmacokinetics*
  • Simvastatin / pharmacokinetics*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lactones
  • Pyrroles
  • Atorvastatin
  • Simvastatin